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Molecular mechanisms linking inflamm...

Yale University.

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Molecular mechanisms linking inflammation, cancer and chemoresistance.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Molecular mechanisms linking inflammation, cancer and chemoresistance./
作者:	Chen, Rui.
面頁冊數:	228 p.
附註:	Advisers: Gil Mor; Harold Behrman.
Contained By:	Dissertation Abstracts International69-05B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3317077
ISBN:	9780549650201

Molecular mechanisms linking inflammation, cancer and chemoresistance.
Chen, Rui.

Molecular mechanisms linking inflammation, cancer and chemoresistance. - 228 p.

Advisers: Gil Mor; Harold Behrman.

Thesis (Ph.D.)--Yale University, 2008.

Chronic inflammation is associated with cancer. The transcription factor NF-kappaB has been found to play an important role in carcinogenesis as well as cancer progression. However, the upstream pathway(s) that leads to cancer-related NF-kappaB activation remains unclear.

ISBN: 9780549650201Subjects--Topical Terms:

1017719
Biology, Molecular.

Molecular mechanisms linking inflammation, cancer and chemoresistance.
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035 $a (UMI)AAI3317077
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100 1 $a Chen, Rui. $3 1025253
245 1 0 $a Molecular mechanisms linking inflammation, cancer and chemoresistance.
300 $a 228 p.
500 $a Advisers: Gil Mor; Harold Behrman.
500 $a Source: Dissertation Abstracts International, Volume: 69-05, Section: B, page: 2922.
502 $a Thesis (Ph.D.)--Yale University, 2008.
520 $a Chronic inflammation is associated with cancer. The transcription factor NF-kappaB has been found to play an important role in carcinogenesis as well as cancer progression. However, the upstream pathway(s) that leads to cancer-related NF-kappaB activation remains unclear.
520 $a In this dissertation I report the identification and characterization of two distinct subtypes of ovarian cancer cells, and their association to chemoresponse. Using Epithelial Ovarian Cancer (EOC) cells isolated from malignant ovarian cancer ascites or ovarian cancer tumors, I described a chemoresistant subtype of EOC cells (Type I EOC cells) characterized by constitutive production of NF-kappaB-dependent pro-inflammatory cytokines, where a functional TLR4-MyD88 pathway serves as a major upstream activator of NF-kappaB. In addition I described in Type I EOC cells the pro-tumor effect of paclitaxel, the first-line drug used for the treatment of ovarian cancer, through activating the TLR4-MyD88-NF-kappaB pathway. Moreover, I also determined that Type I EOC cells were capable of responding to other pro-inflammatory stimuli as well, including the inflammatory cytokine TNF-alpha, which also led to NF-kappaB activation and cytokine production. However, none of the above could be seen in the chemosensitive Type II EOC cells.
520 $a Furthermore, I reported the characterization of IKKbeta as a major player in the determination of the unique phenotype of Type I EOC cells. IKKbeta is differentially expressed in the two subtypes of ovarian cancer cells, and is associated with NF-kappaB activity, cytokine production and resistance to paclitaxel or TNF-alpha mediated apoptosis in Type I EOC cells. My further characterization also identified the microRNA hsa-miR-199a as a direct regulator of IKKbeta expression in EOC cells. Moreover, based on our preliminary studies, I propose that MyD88 could be used as potential markers to identify paclitaxel resistant ovarian tumors.
520 $a My findings described in this dissertation provide new insights for both a better understanding of the molecular mechanisms linking inflammation, cancer and chemoresistance, and also potential novel markers and targets for developing effective diagnosis and treatments for chemoresistant ovarian cancer.
590 $a School code: 0265.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Obstetrics and Gynecology. $3 1020690
650 4 $a Health Sciences, Oncology. $3 1018566
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710 2 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 69-05B.
790 $a 0265
790 1 0 $a Behrman, Harold, $e advisor
790 1 0 $a Mor, Gil, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3317077